Home > Articles > Published articles > Switching From a Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen : |
Date: | 2018 |
Abstract: | Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4 + T cells in both groups (P <. 01). Residual viremia in plasma decreased in the switch group (P =. 03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4 + T cells. EudraCT 2014-004331-39. INDOOR evaluated the effect of switching from boosted protease inhibitor- to dolutegravir-based antiretroviral therapy on the HIV reservoir in peripheral blood and ileum. Residual plasma viremia and soluble CD14 levels decreased, but low-level HIV replication, the HIV reservoir, and immune activation remained unaffected. |
Grants: | Ministerio de Economía y Competitividad FPDI-2013-17134 Agència de Gestió d'Ajuts Universitaris i de Recerca 2013FI_B00275 Ministerio de Educación, Cultura y Deporte FPU15/03698 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Switching ; Dolutegravir ; HIV reservoir ; Ileum biopsies ; Immunological and inflammation markers |
Published in: | Clinical Infectious Diseases, Vol. 69 (december 2018) , p. 1320-1328, ISSN 1537-6591 |
9 p, 1.7 MB |